Lung Cancer

Neha Vapiwala, MD and Charles B. Simone, II, MSIV Abramson Cancer Center of the University of Pennsylvania Last Modified: March 29, 2006

Introduction

Lung cancer is the second most common malignancy in males and females, surpassed in incidence only by prostate and breast cancer, respectively. Moreover, it is the most common cause of cancer death in both genders, in part because it is diagnosed at more advanced stages and in part because management is less successful than breast and prostate cancer. In the US, mortality from lung cancer represents about thirty percent of all cancer-related deaths.

Lung cancer is generally divided into two main types, non-small cell and small cell. This histological classification scheme has significant implications in terms of the origin, natural history and management of these tumors, as outlined below.

Epidemiology and Etiology

Incidence of over 170,000 cases yearly, with a trend of decreasing incidence in men but increasing incidence in women secondary to changes in smoking behaviors. No known racial predilection exists. Mortality of greater than 160,000 deaths in the United States in 2005 [1].

Etiology of most lung cancers is related to chronic cellular damage and DNA mutations from exposure to carcinogens such as cigarette smoke (the cause of 87% of cases), ionizing radiation, radon gas, asbestos, and industrial chemicals.

Hereditary links or molecular genetic defects have not been established.

Risk factors include: exposure to carcinogens, as mentioned above, especially tobacco smoke, which shows a direct link between dose and cancer risk and acts synergistically with other carcinogens to increase risk; history of interstitial lung disease; history of tuberculosis.

Screening in Asymptomatic, High-Risk Population

There has never been a documented decrease in mortality from lung cancer due to screening, and no professional society has endorsed routine screening in high-risk patients.

The yield of screening chest radiography (CXR) is low; sputum cytology has an even lower sensitivity compared to CXR.

Spiral chest CT scan can improve sensitivity, but at this time it is not considered a cost-effective screening test and has not been shown to decrease mortality.

Natural Course and Pathology

Staging: Both a clinical and a pathologic assessment together are critical in the selection of therapy; distinction between clinical stage and pathologic stage should be considered when evaluating reports of survival outcome.

Surgical staging of the mediastinum is considered standard if accurate evaluation of the nodal status is needed to determine therapy.

NSCLC: The Revised International System for Staging Lung Cancer, which employs TNM staging, was adopted in 1997 by the American Joint Committee on Cancer and the Union Internationale Contre le Cancer to provide greater specificity for patient groups and to clarify the classification of multiple tumor nodules (satellite tumor nodules, intrapulmonary ipsilateral metastasis).

SCLC: As occult or overt metastatic disease is usually present at diagnosis, survival is generally not affected by small differences in the amount of locoregional tumor involvement. A simple 2-stage system of limited vs. extensive disease, developed by the Veterans Administration Lung Cancer Study Group, is commonly used.

Patients with medically inoperable Stage I or II disease may be treated with radiation therapy or radiofrequency ablation, performed percutaneously with CT guidance or intraoperatively.

Radiation therapy may be used alone for nonresectable patients, preoperatively (neoadjuvant) to shrink a tumor, or postoperatively (adjuvant) to decrease local recurrence or target positive regional lymph nodes.

Radiation can improve local control in patients with Stage I and II disease and may increase survival in Stage III disease.

Chemotherapy may be used as an adjuvant treatment since many patients treated with surgery alone subsequently develop regional or distant metastases [7]. Additionally, neoadjuvant chemotherapy has been shown to improve disease-free survival when compared to patients treated with surgery alone [8].

Chemoradiation [9, 10, 11, 12, 13] has been shown to increase survival in patients with Stage III inoperaple disease who have a good performance status and minimal weight loss (= 5%).

Chemoradiation therapy given sequentially can decrease the development of distant metastases, while chemoradiation given concurrently can improve locoregional control [3].

Photodynamic therapy (PDT) combines a photosensitizing drug with a specific type of light to kill localized cancer cells. Although PDT has minimal side effects and can be repeated multiple times in the event of tumor recurrence or limited treatment response, PDT generally is only used to treat small, superficial lung lesions. It is also used to palliate obstructing endobronchial lesions.

Late stage NSCLC

Radiation therapy is standard treatment for Stage IIIB patients. When combined with adjuvant cytotoxic chemotherapy the overall 5-year survival rates are improved from the 5% achieved with radiation alone [10].

Unresectable disease should be treated with concurrent chemoradiation, often followed by consolidation chemotherapy in patients with good performance status.

New chemotherapy agents, including paclitaxel (Taxol), docetaxel (Taxotere), topotecan, irinotecan, vinorelbine, or gemcitabine ( Gemzar ® ), may be used in combination with cisplatin or carboplatin in the treatment of advanced NSCLC [14].

Targeted Therapies/Biologic Therapies , new classes of medications that have been specifically designed to function at precise molecular pathways and receptors, are currently being investigated for their use in the treatment of late stage NSCLC. Such therapies, which are often given in conjunction with standard chemotherapeutic agents, include farnesyl transferase inhibitors, signal transduction inhibitors (including the tyrosine kinase inhibitor, erlotinib [Tarceva]), antiangiogenic agents, and monoclonal antibodies (including trastuzumab [Herceptin]).

Early stage SCLC (Limited, M0)

Chemotherapy and local radiation given concurrently can achieve a 14% reduction in the mortality rate when compared to chemotherapy alone [16].

Chemotherapeutic regiments often include cisplatin or carboplatin and etoposide or teniposide.

Radiation therapy given twice daily has been shown to significantly increase survival when compared to standard daily regiments [17].

Prophylactic cranial irradiation remains controversial but can decrease the risk of brain metastasis and result in a 5.4% increase in the rate of survival at three years [18].

Late stage SCLC (Extensive, M1)

The combination of cisplatin or carboplatin with etoposide is the standard of care in the United States for the treatment of extensive SCLC disease.

Alternative treatment strategies include the use of taxanes, topoisomerase I inhibitors (topotecan, irinotecan), gemcitabine or vinorelbine, and high-dose chemotherapy with autologous bone marrow transplantation.

Palliative radiation or chemotherapy for local and distant symptoms are employed to improve patient quality of life [19].